The invention relates to a process for the preparation of 1-[2-(alkoxycarbonyl)ethyl]-1-cyclopentanecarboxylic acid derivatives, the use of which has previously been disclosed in EP-A-0274334 as intermediates for the preparation of certain substituted glutaramide diuretic agents having utility in the treatment of hypertension, heart failure, renal insufficiency and in other disorders.
EP-A-0274234 describes two methods for the preparation of 1-[2-(alkoxycarbonyl)ethyl]-1-cyclopentanecarboxylic acid derivatives by which the dianion derived from cyclopentanecarboxylic acid by treatment with a strong base, e.g. lithium diisopropylamide, is treated with either (i) an acrylate derivative, or (ii) an ester of 3-bromopropanoic acid followed by optional further alkylation as required, to provide the desired products. However, the favored route, involving use of an acrylate derivative, can not be used for certain preferred embodiments of the present invention due to competing elimination reactions.
It has now been discovered that 1-[2-(alkoxycarbonyl)ethyl]-1-cyclopentanecarboxylic acid derivatives may be unexpectedly prepared by the oxidative rearrangement of 2-acyl- or 2-alkoxycarbonyl-cyclohexanone derivatives, offering further commercially important improvements over the existing processes such as ease and lower cost of operation.